Set-up of a Platform for Personalized Diagnosis of Rare Kidney Diseases (NIKE)

NCT ID: NCT06325072

Last Updated: 2024-03-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-09
• Study Completion Date: 2024-06-30

Brief Summary

Chronic kidney disease (CKD) is a major health problem, with steadily increasing incidence and prevalence and the threat of a true "epidemic". Converging evidence suggests a high prevalence of genetic etiology in rare kidney diseases and the list of new disease-causing genes is constantly updated. Recent advances in next-generation sequencing (NGS) technologies have prompted a significant improvement in the diagnosis of rare kidney diseases. Notwithstanding this, NGS generates high numbers of information that need to be properly analysed by the joint efforts of geneticists, nephrologists and bioinformatics in order to integrate clinical and genetic information in a personalized manner. In addition, in selected cases, the contribution of researchers proves essential for the development of experimental models of the disease to study and understand the pathogenic features and propose a personalized therapeutic approach. Such an innovative, integrated diagnostic paradigm is currently available in few centers all over the world and cannot be easily translated in daily clinical practice.

The aim of the study is to set-up an integrated diagnostic algorithm to extend the newest personalized diagnostic and treatment strategies for rare kidney diseases to all patients in the Tuscany region, under 40 years of age with kidney disease. This algorithm will be based on a constant cross-talk between participating centers and a dedicated multidisciplinary team. Diagnostic and therapeutic performances will be validated at European level.

Conditions

Chronic Kidney Diseases

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Pathogenic variants

Variants fitting bioinformatic prioritization criteria for pathogenicity according to ACMG guidelines and the clinical phenotype, and variants already reported in the literature will be defined as pathogenic variants

Group Type: EXPERIMENTAL

Conclusive genetic testing

Intervention Type: DIAGNOSTIC_TEST

Patients will be referred for genetic counseling at the study coordinating center. This will lead to a conclusive genetic diagnosis.

Potentially Pathogenic Variants

Variants fitting bioinformatic prioritization criteria but apparently do not correlate with the clinical phenotype and have not been previously reported in the literature will be defined as potentially pathogenic variants

Group Type: EXPERIMENTAL

Genotype-phenotype correlation for personalized diagnosis

Intervention Type: DIAGNOSTIC_TEST

Patients and their family members will undergo a thorough clinical reassessment at the study coordinating center to identify diagnostic handles of the suspected disease based on the genetic test result (reverse phenotyping). The clinical reassessment could include the performance of additional clinical and instrumental tests, as well as other specialized consultations. This will lead to a conclusive genetic diagnosis in a substantial proportion of cases, cases, who will then be provided with genetic counselling.

Variants of Unknown Significance (VUS)

Variants fitting the phenotype but not fitting bioinformatic prioritization criteria will be defined as variants of uncertain clinical significance (VUS)

Group Type: EXPERIMENTAL

Personalized study of variants of uncertain clinical significance (VUS) through functional studies on 3D organ-on-a-chip

Intervention Type: DIAGNOSTIC_TEST

The investigators will perform functional assessment trough urine derived Renal Progenitor Cells (u-RPC) to establish the role of variants in determining the clinical phenotype.

Interventions

Conclusive genetic testing

Patients will be referred for genetic counseling at the study coordinating center. This will lead to a conclusive genetic diagnosis.

Intervention Type: DIAGNOSTIC_TEST

Genotype-phenotype correlation for personalized diagnosis

Patients and their family members will undergo a thorough clinical reassessment at the study coordinating center to identify diagnostic handles of the suspected disease based on the genetic test result (reverse phenotyping). The clinical reassessment could include the performance of additional clinical and instrumental tests, as well as other specialized consultations. This will lead to a conclusive genetic diagnosis in a substantial proportion of cases, cases, who will then be provided with genetic counselling.

Intervention Type: DIAGNOSTIC_TEST

Personalized study of variants of uncertain clinical significance (VUS) through functional studies on 3D organ-on-a-chip

The investigators will perform functional assessment trough urine derived Renal Progenitor Cells (u-RPC) to establish the role of variants in determining the clinical phenotype.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• family history of kidney disease and/or parental consanguinity;
• extra-renal involvement (e.g., sensorineural hearing loss);
• resistance to treatment (e.g., immunosuppressive);
• metabolic acidosis or metabolic alkalosis in the absence of renal failure;
• ultrasound detection of of at least 2 cystic lesions in each kidney or nephrocalcinosis;
• ultrasound detection of congenital abnormalities of the kidney and urinary tract (CAKUT) and CKD stage ≥ 2 according to KDIGO definition
• informed consent form.

Exclusion Criteria

• age > 40
• refuse to participate to the study

• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Meyer Children's Hospital IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Paola Romagnani

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Azienda Ospedaliero Universitaria Careggi

Florence, , Italy

Meyer Children's Hospital IRCCS

Florence, , Italy

USL Toscana Centro

Florence, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Countries

Italy

Other Identifiers

NIKE

Identifier Type: -

Identifier Source: org_study_id